Between Placebo and Nocebo

Ask a physician about the Placebo effect and depending on his or her poker face, they might betray a little discomfort. This is because the Placebo effect and its counterpart the Nocebo effect(when an otherwise inert intervention causes harm), lie at the very threshold of our knowledge as medical professionals.

In many ways, the entire edifice of modern medicine rests on the Placebo effect. When a pharmaceutical company develops a drug, one of the most important hurdles they must jump is demonstrating that it outperforms a placebo in clinical trials. The theory is that if the drug really works, it will perform better than a placebo, or a fake drug. The problem is that the fake drugs often work. Indeed, placebos have been shown to be remarkably effective at treating a variety of illnesses. Moreover, as pharmaceutical companies well know, subtle differences such as the color or shape of a pill can have a dramatic impact on clinical results. And yet if we admit that the Placebo effect is real and can actually heal people, are we not also devaluing our own interventions? What distinguishes us at that point from a snake oil salesman?

The answer must be science. Science is what distinguishes us from the quackery of the unscrupulous. So we must shine the light of science on the phenomena known as the Placebo and Nocebo effects to better understand their mechanisms of action. Happily, there has been a shift in thinking on this subject over the last decade or so and scientists are finally making strides to better understand the mechanisms of action that underlie these peculiar phenomena.

As it happens, some of the most interesting research on Placebo and Nocebo is being done around the experience of pain. One of the many benefits of the Placebo effect is that it can reduce pain. Recent studies have shown that Naloxone, a drug that interferes with opioid receptors, also has the potential to block the analgesic placebo effect. These studies suggest that the analgesic placebo effect leads to a release of endogenous opioids in the spine which produce relief. Other studies have shown that people who have a propensity for more profound placebo analgesia also have more marked responses to opioids, pointing to a possible genetic component for the Placebo effect. But beyond the molecular mechanisms, we are also learning that expectations play a role. When patients participating in a clinical trial are unwittingly given the placebo pill, they are given the exact same warnings about potential side effects as those taking the real drug. Unfortunately, the Nocebo effect ensures that many of them will actually suffer from these negative side effects, despite the fact that the substance they are taking is totally inert.

We are clearly just beginning to scratch the surface of these fascinating phenomena. But as physicians, we need to be more sensitive to them in our practices. We must harness the Placebo and mitigate against the Nocebo effects in the service of our patients. Finally, we must approach both our patients and our profession with a greater degree of humility.